Danaparoid sodium prevents cerulein-induced acute pancreatitis in rats.
Systemic inflammatory mediators, including the protein high-mobility group box 1 (HMGB1), play an important role in the development of acute pancreatitis. Anticoagulants such as danaparoid sodium (DA) may be able to inhibit sepsis-induced inflammation, but the mechanism of action is not well understood. We hypothesized that DA would act as an inhibitor of inflammation and prevent cerulein-induced acute pancreatitis. Male Wistar rats were used as subjects in this study. Each received a bolus of 50 U/kg of DA or saline-injected into the tail vein, followed by 4 injections of 50 mg/kg cerulean (i.p.) at 1-h intervals. Cytokine (IL-6), NO, and HMGB1 levels in serum and pancreatic tissue were measured after the cerulein injection. Pancreas histopathology and wet-dry ratio significantly improved in the DA-injected (50 U/kg) animals compared with saline-injected rats. Serum and pancreatic HMGB1 levels decreased over time in DA-treated animals. Danaparoid sodium also decreased cytokine, NO, and HMGB1 levels during cerulein-induced inflammation. As a result, DA ameliorated pancreas pathology in the rat model of cerulein-induced acute pancreatitis. This study demonstrates that DA treatment prevents cerulein-induced acute pancreatitis in a rat model. This effect may be mediated through inhibition of cytokines, NO, and HMGB1.
Hagiwara
Satoshi
S
Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan. saku@med.oita-u.ac.jp
Iwasaka
Hideo
H
Uchida
Tomohisa
T
Hasegawa
Akira
A
Asai
Nobuhiko
N
Noguchi
Takayuki
T
D000818:Animals; D015153:Blotting, Western; D002108:Ceruletide / Q000494:pharmacology*; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D003871:Dermatan Sulfate / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000097:blood; D006497:Heparan Sulfate / Q000494:pharmacology*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats
D002108:Ceruletide; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005343:Fibrinolytic Agents; D024243:HMGB1 Protein; D006497:Heparan Sulfate; D015850:Interleukin-6; D016328:NF-kappa B; D009566:Nitrates; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites; D009195:Peroxidase; C035838:danaparoid